US2005065118A1PendingUtilityA1
Organosulfur inhibitors of tyrosine phosphatases
Priority: Oct 16, 2001Filed: Oct 16, 2002Published: Mar 24, 2005
Est. expiryOct 16, 2021(expired)· nominal 20-yr term from priority
Inventors:Jing WangDarryl RideoutKalyanaraman RamnarayanChung-Ying TsaiVenkatachalapathi YalamooriFeiyue WuColin J. LowethHassan M. ElabdellaouiLeah FungThomas Brady
A61P 43/00A61P 9/10A61P 9/00A61P 9/12A61P 3/10A61P 3/04A61P 25/28A61P 27/02A61P 35/00A61K 31/426A61K 31/66A61K 31/429A61K 31/428A61K 31/433A61K 31/41A61P 1/14A61K 31/325A61P 13/12A61K 31/542
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Claims
Abstract
Organosulfur modulators of tyrosine phosphatases and their use in the treatment of disease are disclosed.
Claims
exact text as granted — not AI-modified1 . A method of inhibiting protein tyrosine phosphatase activity which comprises administering to a mammal an effective amount of a compound having the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R1, R2, and R3 are each independently selected from
H, hydroxyl, alkoxy, alkylthio, nitro, amino or amido (each unsubstituted or substituted with alkyl, amino, cycloheteroalkyl, cycloalkyl fluoro, aryl, heteroaryl, cycloheteroalkyl, alkylthio, arylthio, cyano, OR′, OC═OR″, C═O—OR′″, or C═O—NR″″R″″);
small alkyl (C1-C10) (unsubstituted or substituted with alkyl, amino, cycloheteroalkyl, cycloalkyl fluoro, aryl, heteroaryl, cycloheteroalkyl, alkylthio, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , arylthio, cyano, OR″, OC═OR″, C═O—OR′″, or C═O—NR″″R″″);
phenyl and mono and disubstituted (at positions 3 and 4) phenyl (wherein the phenyl ring is independently substituted with alkyl, trifluoromethyl, mono and di halogen atoms, alkylthio, alkoxy, nitro, cyano, morphilino, cyclohexyl, phenyl, phenolic, dioxymethylene, nitro, acetylamino, OR′, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 );
heteroaryl, cycloheteroalkyl and cycloheteroalkyl (each unsubstituted or substituted with alkyl, halogen, alkylthio, alkoxy, or nitro, OR′, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ,);
cycloalkyl (C3-C10) (unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, OC═OR′, C═O—OR″, or C═O—NR′″ R″″);
alkenyl (C1-C10) (unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, OC—OR′, C═O—OR″, or C═O—NR′″R″″);
alkadienyl (C1-C10) (unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, —OC═OR5, —C═O—OR″, C═O—NR′″R″″);
cycloalkenyl (C4-C10), unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, —OC═OR′, —C═O—OR″, C═O—NR′″ R″″;
bicycloalkyl (C5-C12), unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, —OC═OR′, —C═O—OR″, C—O—NR′″R″″;
tricycloalkyl (C8-C14), unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, —OC═OR′, —C═O—OR″, C═O—NR′″R″″;
where
Each R′ is independently:
hydrogen;
alkyl (C1-C10), unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, cyano, aryloxy, cycloalkyl, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
aryl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, cyano, aryloxy, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
heteroaryl, cycloheteroalkyl, cycloheteroalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, cyano, aryloxy, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
cycloalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, cyano, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P—O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
Each R″ is independently
hydrogen,
alkyl (C1-C10), unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl;
aryl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio;
heteroaryl, cycloheteroalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio;
cycloalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl;
Each R′″ is independently
alkyl (C1-C10), unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
aryl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio;
heteroaryl, cycloheteroalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
cycloalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, COOR″, P═O(OR″) 2 , CH 2 P—O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ; and
Each R″″ is independently
alkyl (C1-C10), unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, COOR″, PO(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
aryl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
heteroaryl, cycloheteroalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ; and
cycloalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalky, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
and wherein each of R1, R2 and R3 are linked to their respective core atoms through C, N, O or S of the substiuent group, provided that if R2 is to be linked through O or S, then the core atom S is oxidized.
2 . A method as recited in claim 1 wherein R1 and R2 are taken together with the core unit to which they are attached (formula I) to form a heterocyclic group having formula (II) as follows:
wherein R5 is an amino group with two substituents, where
one substituent is arylcarbonyl, arylmethylcarbonyl, arylsulfonyl, aryldimethyloxycarbonyl, or aryloxymethylcarbonyl, [where the aryl group is phenyl, benzox[c]1,2,5-oxadiazol-5-yl, 1-furyl, 2-furyl 1-naphthyl or 2-naphthyl, unsubstituted or substituted with one or more of the following or their combinations: perfluoroalkyl (C1-C4), alkyl (C1-C4), nitro, alkoxycarbonyl (C1-C4), carboxyl, carboxyalkyl(C1-C4), CF 2 P═O(OH) 2 , NHCOCOOH, phenoxy (unsubstituted or substituted with alkoxy (C1-C4), CF 2 P═O(OH) 2 , NHCOCOOH, COOH, and/or halogen), or phenylalkoxy (C1-C4)], hydrogen, CF 2 P═O(OH) 2 , NHCOCOOH, or a phenyl group [unsubstituted or with one or more of the following substituents or combinations: hydroxy, halogen, nitro, CF 2 P═O(OH) 2 , NHCOCOOH, carboxy, carboxyalkyl(C1-C4), carboxyalkylthio (C1-C6), phenyl, alkyl (C1-C10) or alkoxy (C1-C10) (unsubstituted or substituted with NR1R2, COOH, cycloheteroalkyl), perfluoroalkyl (C1-C4), alkoxycarbonyl (C1-C4), alkylthio (C1-C4), phenylalkoxy (C1-C4), phenylsulfonylamino (each unsubstituted or substituted on phenyl with alkyl (C1-C4)), phenoxy (unsubstituted or substituted on phenyl with nitro, perfluoroalkyl (C1-C4), carboxymethyl, carboxy, CF 2 P═O(OH) 2 , NHCOCOOH, alkoxycarbonylmethyl (C1-C4)), carboxyalkyl(C1-C4), phenylalkylthio (C1-C4, unsubstituted or substituted on phenyl with alkoxy (C1-C4), and/or phenyl), aminosulfonyl, alkylaminosulfonyl (C1-C4), dialkylaminosulfonyl (C1-C4 where the two alkyls unsubstituted or form a heteroalicyclic ring)]; and
the second substituent on the amino group forming R5 is hydrogen, alkyl (C1-C10) or alkoxy (C1-C10) (each unsubstituted or substituted with NR1R2, COOH, CF 2 P═O(OH) 2 , NHCOCOOH, cycloheteroalkyl), naphthylalkyl (C1-C4), phenylalkyl (C1-C4, with the phenyl group unsubstituted or substituted with phenyl, alkyl (C1-C4), halo, amino, amido, keto, CF 2 P═O(OH) 2 , NHCOCOOH, alkyl (C1-C10) or alkoxy (C1-C10) (unsubstituted or substituted with NR1R2, COOH, cycloheteroalkyl), nitro, carboxy, perfluoroalkylthio (C1-C4), halogen, CF 2 P═O(OH) 2 , NHCOCOOH, 1,2,3-thiadiazolyl, and/or alkoxy carbonyl (C1-C4)), alkyl (C1-C10), cycloalkyl (C4-C8, unsubstituted or substituted with alkyl (C1-C4)), or indanyl (unsubstituted or substituted with alkyl (C1-C4)).
3 . A method as recited in claim 2 wherein R3 is
(1) a phenyl group unsubstituted or substituted with one to three of the following and their combinations: halogen, hydroxy, aryloxy, nitro, carboxylic acid, CF 2 P═O(OH) 2 , NHCOCOOH, alkyl (C1-C10) or alkoxy (C1-C10) (unsubstituted or substituted with NR1R2, COOH, cycloheteroalkyl), alkylthio (C1-C4), 2′-hydroxyethoxy, alkoxycarbonylmethoxy (C1-C4), dialkylamino (C1-C4 where the two alkyls can form a heteroalicyclic ring), 2-(dialkylamino)-2-oxoethoxy (C1-C7 where the two alkyls can form a heteroalicyclic ring), difluoromethoxy, perfluoroallyl (C1-C4), perfluoroalkylthio (C1-C4), perfluoroalkoxy (C1-C4), 2-carboxyvinyl, alkanoyl (C1-C5), alkoxycarbonyl (C1-C4), alkanoylamino (C1-C8), benzoylamino (unsubstituted or substituted with one or more perfluoroalkyl group (C1-C4) and/or CF 2 P═O(OH) 2 , NHCOCOOH,), aryl, aryloxy, arylcarbonyl, arylmethoxy, arylmethyl in which the methyl group is substituted with hydroxyl, O(CH 2 ) n COOH (n=1-5), S(CH 2 ) n COOH (n=1-5), (4-carboxy)benzyloxy, (3-carboxybenzyloxy), or the group ═N—O—CH 2 R in which R is carboxyl, alkoxycarbonyl (C1-C4), hydrogen, or phenyl (unsubstituted or substituted with one or more halogens), or the group ═N—NHAr in which Ar is a phenyl (unsubstituted or substituted with one or more alkyl groups (C1-C4), and/or a carboxyl group, and/or CF 2 P═O(OH) 2 , NHCOCOOH), or the group-Y—(CH 2 ) n -Z, where Y is O or S, n is 1, 2, or 3, and Z is hydrogen, methyl, branched alkyl (C3-C5), cycloalkyl (C3-C6), phenyl (unsubstituted or substituted with one or more of the following: halogen, trifluoroalkyl, carboxy, alkoxycarbonyl (C1-C4), CF 2 P═O(OH) 2 , NHCOCOOH, or carboxyl; or (2) a pyridylthio group unsubstituted or substituted with one or more halogen and/or one or more nitro groups, methylenedioxyphenyl, benzo[3,4-c]1,2,5-oxadiazol-5-yl, 4-oxo-3-hydroquinazolin-2-yl, or a group having formula (III) as follows: in which the imidazole ring is unsubstituted or substituted with one or more halogens.
4 . A method as recited in claim 1 wherein R1 and R2 are taken together with the core unit to which they are attached (formula I) to form a heterocyclic group having formula (IV as follows:
wherein R6 and R7 are each independently as defined for R1, R2 and R3.
5 . A method as recited in claim 1 wherein R1 and R2 are linked through an aromatic ring, and taken together with the N═CR3—S unit to which they are attached, form a tricyclic heterocyclic group having formula (V) as follows:
Where R9, R10 and R11 are each independently as defined for R1, R2 and R3.
6 . A method as recited in claim 1 wherein R1 and R2, taken together with the N═CR3—S unit to which they are attached, form a heterocyclic group having formula (VI) as follows:
Wherein R12 and R13 are each independently as defined for R1, R2 and R3.
7 . A method as recited in claim 1 wherein R1 and R3, taken together with the N═C—SR2 unit to which they are attached, form a heterocyclic group having formula (VII) as follows:
Wherein R14 and R15 are each independently as defined for R1, R2 and R3.
8 . A method as recited in claim 1 wherein R1 and R3, taken together with the N═C—SR2 unit to which they are attached, form a bicylic heterocyclic group having formula (VII) as follows:
Wherein R18 and R19 are each independently as defined for R1, R2 and R3.
9 . A method as recited in claim 1 wherein R1, R2 and R3, taken together with the N═C—S unit to which they are attached, form a bicyclic heterocyclic group having formula (IX) as follows:
Wherein R20, R21 and R22 are each independently as defined for R1, R2 and R3.
10 . A method as recited in claim 1 wherein R1, R2 and R3, taken together with the N═C—S unit to which they are attached, form a bicyclic heterocyclic group having formula (X) as follows:
Where R23 and R24 are each independently as defined for R1, R2 and R3.
11 . A pharmaceutical composition which comprises an effective amount of a compound having the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R1, R2, and R3 are each independently selected from
H, hydroxyl, alkoxy, alkylthio, nitro, amino or amido (each unsubstituted or substituted with alkyl, amino, cycloheteroalkyl, cycloalkyl fluoro, aryl, heteroaryl, cycloheteroalkyl, alkylthio, arylthio, cyano, OR′, OC═OR″, C═O—OR′″, or C═O—NR″″R″″);
small alkyl (C1-C10) (unsubstituted or substituted with alkyl, amino, cycloheteroalkyl, cycloalkyl fluoro, aryl, heteroaryl, cycloheteroalkyl, alkylthio, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , arylthio, cyano, OR″, OC═OR″, C═O—OR′″, or C═O—NR″″R″″);
phenyl and mono and disubstituted (at positions 3 and 4) phenyl (wherein the phenyl ring is independently substituted with alkyl, trifluoromethyl, mono and di halogen atoms, alkylthio, alkoxy, nitro, cyano, morphilino, cyclohexyl, phenyl, phenolic, dioxymethylene, nitro, acetylamino, OR′, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 );
heteroaryl, cycloheteroalkyl and cycloheteroallyl (each unsubstituted or substituted with alkyl, halogen, alkylthio, alkoxy, or nitro, OR′, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ,);
cycloalkyl (C3-C10) (unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl alkylthio, arylthio, cyano, P—O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, OC═OR′, C═O—OR″, or C═O—NR′″R″″);
alkenyl (C1-C10) (unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, OC═OR′, C═O—OR″, or C═O—NR′″R″″);
alkadienyl (C1-C10) (unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, —OC═OR5, —C═O—OR″, C═O—NR′″R″″);
cycloalkenyl (C4-C10), unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, —OC═OR′, —C═O—OR″, C═O—NR′″R″″;
bicycloalkyl (C5-C12), unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, —OC═OR′, —C═O—OR″, C═O—NR′″R″″;
tricycloalkyl (C8-C14), unsubstituted or substituted with alkyl, fluoro, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, alkylthio, arylthio, cyano, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 , OR′, —OC═OR′, —C═O—OR″, C═O—NR′″R″″;
where
Each R′ is independently:
hydrogen;
alkyl (C1-C10), unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, cyano, aryloxy, cycloalkyl, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
aryl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, cyano, aryloxy, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
heteroaryl, cycloheteroalkyl, cycloheteroalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, cyano, aryloxy, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
cycloalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl, cyano, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
Each R″ is independently
hydrogen,
alkyl (C1-C10), unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, cycloheteroalkyl;
aryl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio;
heteroaryl, cycloheteroalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio;
cycloalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl;
Each R′″ is independently
alkyl (C1-C10), unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
aryl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio;
heteroaryl, cycloheteroalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
cycloalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ; and
Each R″″ is independently
alkyl (C1-C10), unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalkyl, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
aryl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
heteroaryl, cycloheteroalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ; and
cycloalkyl, unsubstituted or substituted with alkyl, keto, fluoro, alkoxy, alkylthio, aryl, heteroaryl, cycloheteroalky, COOR″, P═O(OR″) 2 , CH 2 P═O(OR″) 2 , CF 2 P═O(OR″) 2 , NHCOCOOR″, CH(COOR″) 2 ;
and wherein each of R1, R2 and R3 are linked to their respective core atoms through C, N, O or S of the substiuent group, provided that if R2 is to be linked through O or S, then the core atom S is oxidized.
12 . A pharmaceutical composition as recited in claim 11 wherein R1 and R2 are taken together with the core unit to which they are attached (formula I) to form a heterocyclic group having formula (II) as follows:
wherein R5 is an amino group with two substituents, where
one substituent is arylcarbonyl, arylmethylcarbonyl, arylsulfonyl, aryldimethyloxycarbonyl, or aryloxymethylcarbonyl, [where the aryl group is phenyl, benzox[c]1,2,5-oxadiazol-5-yl, 1-furyl, 2-furyl 1-naphthyl or 2-naphthyl, unsubstituted or substituted with one or more of the following or their combinations: perfluoroalkyl (C1-C4), alkyl (C1-C4), nitro, alkoxycarbonyl (C1-C4), carboxyl, carboxyalkyl(C1-C4), CF 2 P═O(OH) 2 , NHCOCOOH, phenoxy (unsubstituted or substituted with alkoxy (C1-C4), CF 2 P═O(OH) 2 , NHCOCOOH, COOH, and/or halogen), or phenylalkoxy (C1-C4)], hydrogen, CF 2 P═O(OH) 2 , NHCOCOOH, or a phenyl group [unsubstituted or with one or more of the following substituents or combinations: hydroxy, halogen, nitro, CF 2 P═O(OH) 2 , NHCOCOOH, carboxy, carboxyalkyl(C1-C4), carboxyalkylthio (C1-C6), phenyl, alkyl (C1-C10) or alkoxy (C1-C10) (unsubstituted or substituted with NR1R2, COOH, cycloheteroalkyl), perfluoroalkyl (C1-C4), alkoxycarbonyl (C1-C4), alkylthio (C1-C4), phenylalkoxy (C1-C4), phenylsulfonylamino (each unsubstituted or substituted on phenyl with alkyl (C1-C4)), phenoxy (unsubstituted or substituted on phenyl with nitro, perfluoroalkyl (C1-C4), carboxymethyl, carboxy, CF 2 P═O(OH) 2 , NHCOCOOH, alkoxycarbonylmethyl (C1-C4)), carboxyalkyl(C1-C4), phenylalkylthio (C1-C4, unsubstituted or substituted on phenyl with alkoxy (C1-C4), and/or phenyl), aminosulfonyl, alkylaminosulfonyl (C1-C4), dialkylaminosulfonyl (C1-C4 where the two alkyls unsubstituted or form a heteroalicyclic ring)]; and
the second substituent on the amino group forming R5 is hydrogen, alkyl (C1-C10) or alkoxy (C1-C10) (each unsubstituted or substituted with NR1R2, COOH, CF 2 P═O(OH) 2 , NHCOCOOH, cycloheteroalkyl), naphthylalkyl (C1-C4), phenylalkyl (C1-C4, with the phenyl group unsubstituted or substituted with phenyl, alkyl (C1-C4), halo, amino, amido, keto, CF 2 P═O(OH) 2 , NHCOCOOH, alkyl (C1-C10) or alkoxy (C1-C10) (unsubstituted or substituted with NR1R2, COOH, cycloheteroalkyl), nitro, carboxy, perfluoroalkylthio (C1-C4), halogen, CF 2 P═O(OH) 2 , NHCOCOOH, 1,2,3-thiadiazolyl, and/or alkoxy carbonyl (C1-C4)), alkyl (C1-C10), cycloalkyl (C4-C8, unsubstituted or substituted with alkyl (C1-C4)), or indanyl (unsubstituted or substituted with alkyl (C1-C4)).
13 . A pharmaceutical composition as recited in claim 12 wherein R3 is
(1) a phenyl group unsubstituted or substituted with one to three of the following and their combinations: halogen, hydroxy, aryloxy, nitro, carboxylic acid, CF 2 P═O(OH) 2 , —NHCOCOOH, alkyl (C1-C10) or alkoxy (C1-C10) (unsubstituted or substituted with NR1R2, COOH, cycloheteroalkyl), alkylthio (C1-C4), 2′-hydroxyethoxy, alkoxycarbonylmethoxy (C1-C4), dialkylamino (C1-C4 where the two alkyls can form a heteroalicyclic ring), 2-(dialkylamino)-2-oxoethoxy (C1-C7 where the two alkyls can form a heteroalicyclic ring), difluoromethoxy, perfluoroalkyl (C1-C4), perfluoroalkylthio (C1-C4), perfluoroalkoxy (C1-C4), 2-carboxyvinyl, alkanoyl (C1-C5), alkoxycarbonyl (C1-C4), alkanoylamino (C1-C8), benzoylamino (unsubstituted or substituted with one or more perfluoroalkyl group (C1-C4) and/or CF 2 P═O(OH) 2 , NHCOCOOH,), aryl, aryloxy, arylcarbonyl, arylmethoxy, arylmethyl in which the methyl group is substituted with hydroxyl, O(CH 2 ) n COOH (n=1-5), S(CH 2 ) n COOH (n=1-5), (4-carboxy)benzyloxy, (3-carboxybenzyloxy), or the group ═N—O—CH 2 R in which R is carboxyl, alkoxycarbonyl (C1-C4), hydrogen, or phenyl (unsubstituted or substituted with one or more halogens), or the group ═N—NHAr in which Ar is a phenyl (unsubstituted or substituted with one or more alkyl groups (C1-C4), and/or a carboxyl group, and/or CF 2 P═O(OH) 2 , NHCOCOOH), or the group-Y—(CH 2 ) n -Z, where Y is O or S, n is 1, 2, or 3, and Z is hydrogen, methyl, branched alkyl (C3-C5), cycloalkyl (C3-C6), phenyl (unsubstituted or substituted with one or more of the following: halogen, trifluoroalkyl, carboxy, alkoxycarbonyl (C1-C4), CF 2 P═O(OH) 2 , NHCOCOOH, or carboxyl; or (2) a pyridylthio group either unsubstituted or substituted with one or more halogen and/or one or more nitro groups, methylenedioxyphenyl, benzo[3,4-c]1,2,5-oxadiazol-5-yl, 4-oxo-3-hydroquinazolin-2-yl, or a group having formula (III) as follows: in which the imidazole ring is unsubstituted or substituted with one or more halogens.
14 . A pharmaceutical composition as recited in claim 11 wherein R1 and R2 are taken together with the core unit to which they are attached (formula I) to form a heterocyclic group having formula (IV) as follows:
wherein R6 and R7 are each independently as defined for R1, R2 and R3.
15 . A pharmaceutical composition as recited in claim 11 wherein R1 and R2 are linked through an aromatic ring, and taken together with the N═CR3—S unit to which they are attached, form a tricyclic heterocyclic group having formula (V) as follows:
Where R9, R10 and R11 are each independently as defined for R1, R2 and R3.
16 . A pharmaceutical composition as recited in claim 11 wherein R1 and R2, taken together with the N═CR3—S unit to which they are attached, form a heterocyclic group having formula (VI) as follows:
Wherein R12 and R13 are each independently as defined for R1, R2 and R3.
17 . A pharmaceutical composition as recited in claim 11 wherein R1 and R3, taken together with the N═C—SR2 unit to which they are attached, form a heterocyclic group having formula (VII) as follows:
Wherein R14 and R15 are each independently as defined for R1, R2 and R3.
18 . A pharmaceutical composition as recited in claim 11 wherein R1 and R3, taken together with the N═C—SR2 unit to which they are attached, form a bicylic heterocyclic group having formula (VIII) as follows:
Wherein R18 and R19 are each independently as defined for R1, R2 and R3.
19 . A pharmaceutical composition as recited in claim 11 wherein R1, R2 and R3, taken together with the N═C—S unit to which they are attached, form a bicyclic heterocyclic group having formula (IX) as follows:
Wherein R20, R21 and R22 are each independently as defined for R1, R2 and R3.
20 . A pharmaceutical composition as recited in claim 11 wherein R1, R2 and R3, taken together with the N═C—S unit to which they are attached, form a bicyclic heterocyclic group having formula (X) as follows:
Where R23 and R24 are each independently as defined for R1, R2 and R3.
StructureNameTable
Molecular Structure
Molecular Name
N-(4-biphenyl-4-yl-thiazol-2-yl)-4-bromo-benz- amide
N2-(4-fluorophenyl)-5-(2-chlorophenyl)-1,3,4- thiadiazol-2-amine
N2-(3,4-dichlorophenyl)-5-(3-nitrophenyl)-1,3,4- thiadiazol-2-amine
2-[[5-(4-fluoroanilino)-1,3,4-thiadiazol-2- yl]thio]-1-(2-naphthyl)ethan-1-one
2-(4-chlorophenyl)-6-[3-(trifluoromethyl)phenyl]- 7aH-azolidino[3,4-e]1,3-thiazine-5,7-dione
4-chloro-N-[6-phenyl-5-(trifluoromethyl)thieno[3,2- d][1,3]thiazol-2-yl]benzamide
N-[2-(4-chlorophenyl)-6-methyl(1,3-thiazolino[3,2- d]1,2,4-triazol-5-yl)](phenylamino)carboxamide
3,6-di(4-chlorophenyl)[1,2,4]triazol[3,4-b][1,3,4]thiadiazole
2-{4-amino-5-[(2,4-dimethylphenyl)carbonyl]thiopheno[3,2-d]isothiazol-3-ylthio}-1-(2,4-dimethylphenyl)ethan-1-one
[(2,4-dichlorophenyl)amino]-N-[2-(4-chloro- phenyl)-6-methyl(1,3-thiazolino[3,2-d]1,2,4-triazol-5-yl)]carboxamide
[2-(2,4-dichlorophenyl)hydrazino]-N-[2-(4-chloro- phenyl)-6-methyl(1,3-thiazolino[3,2-d]1,2,4-triazol-5-yl)]carboxamide
4-=[2-(4-chlorophenyl)[1,3]thiazolo[3,2-B][1,2,4]triazol-6-yl]benzene-1,3-diol
2-{5-[(2,6-dichlorophenyl)methylthio](1,3,4- thiadiazol-2-ylthio)}-5-bromo-3-nitropyridine
(2-anilino-1,3-thiazol-5-yl)(phenyl)methanone
(2-anilino-1,3-thiazol-5-yl)(4-bromo- phenyl)methanone
(2-anilino-1,3-thiazol-5-yl)(3,4-dichloro- phenyl)methanone
ethyl 2-[2-(3,4-dichloroanilino)-1,3-thiazol- 4-yl]benzenecarboxylate
[2-(4-chlorophenyl)-1,3-thiazol-5-yl](3,4- dichlorophenyl)methanone
6-(4-chlorophenyl)-2-phenylimidazolo[2,1- b]1,3,4-thiadiazoline
6-(4-bromophenyl)-2-phenylimidazolo[2,1- b]1,3,4-thiadiazoline
1-(4-nitrophenyl)-2-[5-(4-pentylphenyl)(4H- 1,2,4-triazol-3-ylthio)]ethan-1-one
2,4-difluorophenylthio 2-(4-chlorophenyl)-6- methyl(1,3-thiazolino[3,2-d]1,2,4-triazol-5-yl) ketone
N2-(4-bromo-3-methylphenyl)-5-(2-phenoxy-3- pyridyl)-1,3,4-thiadiazol-2-amine
N-(3,4-dichlorophenyl)-2-(2,4-diphenyl-1,3- thiazol-5-yl)acetamide
2,4-difluorophenylthio 2-(4-chlorophenyl)-6- methyl(1,3-thiazolino[3,2-d]1,2,4-5-yl) ketone
N2-(2,4,5-trichlorophenyl)-8h-indeno[1,2-d][1,3]thiazol-2-amin hydrobromide
(3,5-dichlorophenyl)[5-(4-chlorophenyl)(1,3- thiazol-2-yl)]amine
N2-(2,4,5-trichlorophenyl)-4-(3-nitrophenyl)-1,3- thiazol-2-amine
(5-(2H,3H,4H-benzo[3,4-b]1,4-dioxepin-7-yl)(1,3- thiazol-2-yl))[3,5-bis(trifluoromethyl)phenyl]amine
N-(4-[1,1′-biphenyl]-4-yl-1,3-thiazol-2-yl)- 5-chloro-2-hydroxybenzamide
N1-[4-(2-naphthyl)-1,3-thiazol-2-yl]-5-bromo-2- hydroxybenzamide
N-[4-(3,4-dichlorophenyl)(1,3-thiazol-2-yl)]-3- pyridylcarboxamide
3-{2-[aza(4-bromo-3-chlorophenyl)methylene]-3- benzyl(1,3,4-thiadiazolin-5-yl)}-1-phenoxybenzene
(4-bromo-3-chlorophenyl)benzyl[5-(3-phenoxyphenyl) (1,3,4-thiadiazol-2-yl)]amine
2-{5-[(4-benzo-3-chlorophenyl)amino]-1,3,4- thiadiazol-2-yl}-3-hydroquinazolin-4-one
(5-benzo[3,4-c]1,2,5-oxadiazol-5-yl(1,3,4- thiadiazol-2-yl))(4-bromo-3-chlorophenyl)amine
(3-bromophenyl)[5-(3-{[3-(trifluoromethyl)- phenyl]methoxy}phenyl)(1,3,4-thiadiazol-2-yl)]amine
ethyl 4-{[5-(4-phenoxyphenyl)-1,3,4-thiadiazol-2- yl]amino}benzoate
(3,4-dichlorophenyl)[5-(3-{[4-(tert-butyl)phenyl]methoxy}phenyl)(1,3,4-thiadiazol-2-yl)]{[4-(tertbutyl)phenyl]methyl}amine
methyl-3-(3-{5-[(3,4-dichlorophenyl)amino]-1,3,4- thiadiazol-2-yl}phenoxy)benzoate
3-(3-{5-[(3,4-dichlorophenyl)amino]-1,3,4-thiadiazol- 2-yl}phenoxcy)benzoic acid
5-{5-[(3,4-dichlorophenyl)amino](1,3,4-thiadiazol- 2-yl)}-3-[3-(trifluoromethyl)phenoxy] phenol
(3,4-dichlorophenyl){5-[3-(3-nitrophenoxy)phenyl](1,3,4-thiadiazol-2-yl)}amine
2-[3-(3-{5-[(3,4-dichlorophenyl)amino]-1,3,4- thiadiazol-2-yl}phenoxy)phenyl]acetic acid
4-(3-{5-[(3,4-dichlorophenyl)amino]-1,3,4- thiadiazol-2-yl}phenoxy)phenol
(3,4-dichlorophenyl)[5-(3-{[3-(trifluoro- methoxy)phenyl]methoxy}phenyl)(1,3,4-thiadiazol-2-yl)]amine
2-[4-(phenylmethoxy)phenyl]-N-(5-{3-[3-(tri- fluoromethyl)phenoxy]phenyl}(1,3,4-thiadiazol-2-yl))acetamide
naphthyl-N-(5-{3-[3-(trifluoromethyl)phenoxy]- phenyl}(1,3,4-thiadiazol-2-yl))carboxamide
3-[(3-{5-[(3,4-dichlorophenyl)amino](1,3,4- thiadiazol-2-yl)}phenyl)[3-(trifluoromethyl)phenyl]methylthio]propanoic acid
ethyl 2-[(3-{5-[(3,4-dichlorophenyl)amino]- (1,3,4-thiadiazol-2-yl)}phenyl)[3-(trifluoromethyl)phenyl]meethoxy]acetate
2-[(3-{5-[(3,4-dichlorophenyl)amino](1,3,4- thiadiazol-2-yl)}phenyl)[3-(trifluoromethyl)phenyl]methoxy]acetic acid
2-[4-(tert-butyl)phenoxy]-N-(5-{3-[3-(tri- fluoromethyl)phenoxy]phenyl}(1,3,4-thiadiazol-2-yl))acetamide
[2-(4-methoxyphenoxy)-5-nitrophenyl]-N-(5-{3- [3-(trifluoromethyl)phenoxy]phenyl}(1,3,4-thiadiazol-2-yl))carboxamide
[5-(3,5-dichlorophenoxy)(2-furyl)]-N-(5-{3-[3- (trifluoromethyl)phenoxy]phenyl}(1,3,4-thiadiazol-2-yl))carboxamide
(3-nitrophenyl)-N-(5-{3-[3-(trifluoromethyl)phen- oxy]phenyl}(1,3,4-thiadiazol-2-yl))carboxamide
meethyl 3-(azaq{5-(3-ethoxyphenyl)-3-[(4-phenyl- phenyl)methyl]*1,3,4-thiazolidin-2-ylidene)}methyl)benzoate
3-(3-{5-[(3,4-dichlorophenyl)amino]-1,3,4-thia- diazol-2-yl}phenoxy)benzenecarbonitrile
3-(3-{5-[(3,4-dichlorophenyl)amino]-1,3,4-thia- diazol-2-yl}phenoxy)benzenecarbonitrile
{5-[3-(3-(1H-1,2,3,4-tetrazol-5-yl)phenoxy)phenyl]- (1,3,4-thiadiazol-2-yl)}(3,4-dichlorophenyl)amine
[3-(3-{5-[(3,4-dichlorophenyl)amino](1,3,4-thia- diazol-2-yl)}phenoxy)phenyl]-N-(1,3-dioxolan-2-ylmethyl)carboxamide
3-{5-[(3,4-dichlorophenyl)amino](1,3,4-thiadiazol- 2-yl)}phenyl 3-(trifluoromethyl)phenyl ketone
(3-bromophenyl)[2-(3-nitrophenyl)(1,3-thiazol-5- yl)]amine
N-(3-{5-[(3-bromophenyl)amino](1,3,4-thiadiazol- 2-yl)}phenyl)-4-methylpentanamide
[5-(3-ethoxyphenyl)(1,3,4-thiadiazol-2-yl)][4- (3-methylbutylthio)phenyl]amine
(3-{5-[(3-bromophenyl)aqmino](1,3,4-thiadiazol- 2-yl)}phenyl)(naphthylsulfonyl)amine
3-{2-[aza(3,4-dichlorophenyl)methylene]-3- methyl(1,3,4-thiadiazolin-5-yl)}-1-[3-(trifluoromethyl)phenoxy]benzene
(3,4-dichlorophenyl)methyl(5-{3-[3-(trifluoro- methyl)phenopxy]phenyl}(1,3,4-thiadiazol-2-yl))amine
3-methoxy-1-[6-(4-phenylphenyl)imidazolo[2,1- b]1,3,4-thiadiazolin-2-yl]benzene
1-{6-[3-(2,4-dichlorophenyl)isoxazol-5-yl]- imidazolo[2,1-b]1,3,4-thiadiazoln-2-yl}-3-methoxybenzene
2-(3-nitrophenyl)-6-(4-phenylphenyl)imidazolo[2,1- b]1,3,4-thiadiazoline
6-(2H,3H,4H-benzo[b]1,4-dioxepan-7-yl)-2-(3-nitro- phenyl)imidazolo[2,1-b]1,3,4-thiadiazoline
{3-[(4-methoxyphenyl)methylthio]phenyl}[5- (3-nitrophenyl)(1,3,4-thiadiazol-2-yl)]amine
[5-(3-methoxyphenyl)(1,3,4-thiadiazol-2-yl)]{3- [(4-phenylphenyl)methylthio]phenyl}amine
[5-(3-ethoxyphenyl)(1,3,4-thiadiazol-2-yl)]{3- [(4-phenylphenyl)methylthio]phenyl}amine
[5-(3-nitrophenyl;)(1,3,4-thiadiazol-2-yl)]{3- [(4-phenylphenyl)methylthio]phenyl}amine
3-[3-(3-{5-[(3,4-dichlorophenyl)amino]-1,3,4- thiadiazol-2-yl}phenoxy)phenyl]propanoic acid
{5-[3,5-bis(phenylmethoxy)phenyl](1,3,4-thia- diazol-2-yl)}[3-(3-phenylpropylthio)phenyl]amine
{5-[3,5-bis(phenylmethoxy)phenyl](1,3,4-thia- diazol-2-yl)}{3-[(2-phenylphenyl)methylthio]phenyl}amine
{3-[(2-phenylphenyl)methylthio]phenyl}{5- [2-(trifluoromethyl)phenyl](1,3,4-thiadiazol-2-yl)}amine
[5-(3-nitrophenyl)(1,3,4-thiadiazol-2-yl)][3-(3- phenylpropylthio)phenyl]amine
3-{4-[5-({3-[(2-phenylphenyl)methylthio]- phenyl}amino)(1,3,4-thiadiazol-2-yl)]phenyl}prop-2-enoic acid
4-({5-[3,5-bis(phenylmethoxy)phenyl]-1,3,4-thia- diazol-2-yl}amino)benzoic acid
2-{4-[3-({5-[3,5-bis(phenylmethoxy)phenyl]- 1,3,4-thiadiazol-2-yl}amino)phenoxy]phenyl}acetic acid
(3-bromophen yl)[5-(3-nitrophenyl)(1,3-thiazol-2- yl)]amine
methyl 4-{[(3,4-dichlorophenyl)(5-{3-[3-(tri- fluoromethyl)phenoxy]phenyl}(1,3,4-thiadiazol-2-yl))amino]methyl}benzoate
4-{[(3,4-dichlorophenyl)(5-{3-[3-(trifluoro- methyl)phenoxy]phenyl}(1,3,4-thiadiazol-2-yl))amino]methyl}benzoic acid
(3,4-dichlorophenyl)(5-{3-[3-(oxymethyl)phenoxy]- phenyl}(1,3,4-thiadiazol-2-yl))amine
1-(4-{[5-(3-nitrophenyl)-1,3,4-thiadiazol-2-yl]- amino}phenyl)ethan-1-one
ethyl 2-(3-{5-[(3-bromophenyl)amino]-1,3,4-thia- diazol-2-yl}phenoxy)acetate
[4-(4-nitrophenyl)(1,3-thiazol-2-yl)](4-phenoxy- phenyl)amine
(4-bromo-3-chlorophenyl)[5-(4-ethoxyphenyl)(1,3,4-thia- diazol-2-yl)]amine
(3-bromophenyl)[5-(3-nitrophenyl)(1,3,4-thiadiazol- 2-yl)]benzylamine
2-[aza-(3-bromophenyl)methylene]-5-(3-nitro- phenyl)-3-benzyl-1,3,4-thiadiazoline
[5-(3,4-dimethoxyphenyl)(1,3,4-thiadiazol-2- yl)](4-bromo-3-chlorophenyl)amine
4-{5-[(4-bromo-3-chlorophenyl)amino]-1,3,4- thiadiazol-2-yl}benzene-1,2-diol
(4-bromo-3-chlorophenyl)[5-(3-phenoxyphenyl)(1,3,4- thiadiazol-2-yl)]amine
(4-{5-[(4-bromo-3-chlorophenyl)amino](1,3,4- thiadiazol-2-yl)}phenyl)diethylamine
(4-bromo-3-chlorophenyl)[5-(3-0methylphenyl)(1,3,4- thiadiazol-2-yl)]amine
(naphthylmethyl)[5-(3-nitrophenyl)(1,3,4-thiadiazol- 2-yl)]amine
(3,4-dichlorophenyl)[5-(4-phenylphenyl)(1,3,4-thia- diazol-2-yl)]amine
(4-{5-[(3,4-dichlorophenyl)amino](1,3,4-thia- diazol-2-yl)}phenyl)dimethyamine
(3,4-dichlorophenyl)[5-(4-methylthiophenyl)(1,3,4-thia- diazol-2-yl)]amine
methyl-3-({2-[aza(3,4-dichlorophenyl)methylene]- -(3-ethoxyphenyl)-1,m3,4-thiadiazol-3-yl}methyl)benzoate
(3,4-dichlorophenyl)[5-(3-ethoxyphenyl)(1,3,4-thia- diazol-2-yl)][(4-phenylphenyl)methyl]amineethyl)benzoate
(3,4-dichlorophenyl){[4-(tert-butyl)phenyl]- methyl}[5-(3-ethoxyphenyl)-1,3,4-thiadiazol-2-yl)]amine
1-({2-[aza(3,4-dichlorophenyl)methylene]-5-(3- ethoxyphenyl)(1,3,4-thiadiazolin-3-yl)}methyl)-3-methoxybenzene
(3,4-dichlorophenyl)[5-(3-ethoxyphenyl)(1,3,4-thia- diazol-2-yl)][(3-nitrophenyl)methyl]amine
3-{2-[aza(3,4-dichlorophenyl)methylene]-3-(2- naphthylmethyl)(1,3,4-thiadiazolin-5-yl)}-1-ethoxybenzene
(3,4-dichlorophenyl)[5-(3-ethoxyphenyl)(1,3,4-thia- diazol-2-yl)](2-naphthylmethyl)amine
(3,4-dichlorophenyl){5-[3-(4-methoxyphenoxy)- phenyl](1,3,4-thiadiazol-2-yl)}-amine
(3,4-dichlorophenyl){5-[3-(4-methylphenoxy)- phenyl](1,3,4-thiadiazol-2-yl)}amine
(3,4-dichlorophenyl){5-[3-(3,5-dichlorophenoxy)- phenyl](1,3,4-thiadiazol-2-yl)}amine
(3,4-dichlorophenyl){5-[3-(3,4-dichlorophenoxy)- phenyl](1,3,4-thiadiazol-2-yl)}amine
(3,4-dichlorophenyl)(5-{3-[3-(trifluoromethyl)- phenoxy]phenyl}(1,3,4-thiadiazol-2-yl))amine
(5-(2H-benzo[d]1,3-dioxolan-5-yl)(1,3,4-thia- diazol-2-yl))(3,4-dichlorophenyl)amine
[(4-{[5-(3-nitrophenyl)-1,3,4-thiadiazol-2- yl]amino}phenyl)sulfonyl]piperidine
(4-bromo-3-chlorophenyl)[5-(3-nitrophenyl)(1,3,4- thiadiazol-2-yl)]amine
[5-(3-nitrophenyl)(1,3,4-thiadiazol-2-yl)]- (2,3,4,5-tetrachlorophenyl)amine
(3-chloro-4-methylphenyl)[5-(3-nitrophenyl)- (1,3,4-thiadiazol-2-yl)]amine
(4-methylphenyl)[5-(3-nitrophenyl)(1,3,4-thia- diazol-2-yl)]amine
[4-(methylethyl)phenyl][5-(3-nitrophenyl)- (1,3,4-thiadiazol-2-yl)]amine
(4-butylphenyl)[5-(3-nitrophenyl)(1,3,4-thia- diazol-2-yl)]amine
(4-decylphenyl)[5-(3-nitrophenyl)(1,3,4-thia- diazol-2-yl)]amine
[5-(3-nitrophenyl)(1,3,4-thiadiazol-2-yl)]- [4-(4-nitrophenoxy)phenyl]amine
(3-methylphenyl)[5-(3-nitrophenyl)(1,3,4-thia- diazol-2-yl)]amine
[(4-{[5-(3-methoxyphenyl)-1,3,4-thiadia- zol-2-yl]amino}phenyl)sulfonyl]piperidine
[(4-{[5-(3-methylphenyl)-1,3,4-thiadia- zol-2-yl]amino}phenyl)sulfonyl]piperidine
(5-chloro-2,4-dimethoxyphenyl)[5-(3-nitro- phenyl)(1,3,4-thiadiazol-2-yl)]amine
(3-chloro-4-methylphenyl){5-[3-(phenylmeth- oxy)phenyl](1,3,4-thiadiazol-2-yl)}amine
(3-chloro-4-methylphenyl)[5-(4-morpholin-4-yl- 3-nitrophenyl)(1,3,4-thiadiazol-2-yl)]amine
2-(3-{5-[(3-chloro-4-methylphenyl)amino]- 1,3,4-thiadiazol-2-yl}phenoxy)ethan-1-ol
(3-chloro-4-methylphenyl){5-[4-(trifluoro- methylthio)phenyl](1,3,4-thiadiazol-2-yl)}amine
[(4-{[5-(4-bromo-3-chlorophenyl)-1,3,4-thia- diazol-2-yl]amino}phenyl)sulfonyl]piperidine
[(4-{[5-(3-bromo-4-chlorophenyl)-1,3,4-thia- diazol-2-yl]amino}phenyl)sulfonyl]piperidine
(3-chloro-4-methylphenyl){5-[3-(trifluorometh- oxy)phenyl](1,3,4-thiadiazol-2-yl)}amine
(5-{3-[4-(tert-butyl)phenoxy]phenyl}(1,3,4- thiadiazol-2-yl))(3-chloro-4-methylphenyl)amine
(3,4-dichlorophenyl){5-[4-methoxy-3-(phenylmeth- oxy)phenyl](1,3,4-thiadiazol-2-yl)}amine
(3,4-dichlorophenyl){5-[4-(trifluoromethoxy)- phenyl](1,3,4-thiadiazol-2-yl)}amine
(3,4-dichlorophenyl)[5-(4-butoxyphenyl)(1,3,4-thia- diazol-2-yl)]amine
2-(3-{5-[(3,4-dichlorophenyl)amino](1,3,4-thia- diazol-2-yl)}phenoxy)-1-(4-methylpiperidyl)ethan-1-one
(5-{3-[4-(tert-butyl)phenoxy]phenyl}(1,3,4- thiadiazol-2-yl))indan-2-ylamine
(5-{3-[4-(tert-butyl)phenoxy]phenyl}(1,3,4- thiadiazol-2-yl))(3,3,5-trimethylcyclohexyl)amine
(5-{3-[4-(tert-butyl)phenoxy]phenyl}(1,3,4- thiadiazol-2-yl))(methylhexyl)amine
(5-{3-[3-(trifluoromethyl)phenoxy]phenyl}- (1,3,4-thiadiazol-2-yl))(3,3,5-trimethylcyclohexyl)amine
(4-bromo-3-chlorophenyl)[5-(3-phenoxyphenyl)(1,3,4- thiadiazol-2-yl)]amine
(3-bromophenyl)[5-(2-nitrophenyl)(1,3-thiazol-2- yl)]amine
(3-bromophenyl)[4-(4-chloro-3-meethylphenyl)(1,3- thiazol-2-yl)]amine
(3-bromophenyl)[4-(3-methoxyphenyl)(1,3-thiazol- 2-yl)]amine
(4-{2-[(3,4-dichlorophenyl)amino](1,3-thia- zol-4-yl)}phenyl)diethylamine
N-{2-aza-2-(3-bromophenyl)-1-[(4-phenylphenyl)- methylthio]vinyl}[3-(trifluoromethyl)phenyl]carboxamide
(2Z)-2-aza-3-[(3,4-dichlorophenyl)amino]-1-(3- methoxyphenyl)-3-{[3-(trifluoromethylthio)phenyl]methylthio}prop-2-en-1-one
(3,4-dichlorophenyl)[4-(4-pyrrolidinylphenyl)(1,3- thiazol-2-yl)]amine
4-{2-[(3,4-dichlorophenyl)amino]-1,3-thiazol- 4-yl}benzenecarbonitrile
(3-bromophenyl)[4-(3-chloro-4-methylphenyl)-5- methyl(1,3-thiazol-2-yl)]amine
(3-bromophenyl)[4-(4-methylphenyl)(1,3-thiazol- 2-yl)]amine
3-{2-[(3-bromophenyl)amino]-1,3-thiazol-4- yl}phenyl benzoate
4-{2-[(3-bromophenyl)amino]-1,3-thiazol-4- yl}phenyl benzoate
[3-(trifluoromethyl)phenyl]-N-(5-{3-[3- (trifluoromethyl)phenoxy]phenyl}(1,3,4-thiadiazol-2-yl))carboxamide
N-{2-aza-2-(3,4-dichlorophenyl)-1-[(4-(1,2,3- thiadiazol-4-yl)phenyl)methylthio]vinyl}[3-(trifluoromethyl)phenyl]carboxamide
N-{2-aza-2-(3,4-dichlorophenyl)-1-[(4-phenyl- phenyl)methylthio]vinyl}[3-(trifluoromethyl)phenyl]carboxamide
N-{2-aza-2-(3-bromophenyl)-1-[(4-(1,2,3-thia- diazol-4-yl)phenyl)methylthio]vinyl}[3-(trifluoromethyl)phenyl}carboxamide
(3-{5-[(3,4-dichlorophenyl)amino](1,3,4-thia- diazol-2-yl)}phenyl)[3-(trifluoromethyl)phenyl]methan-1-ol
(3,4-dichlorophenyl)[5-(3-(ethoxy[3-(trifluoro- methyl)phenyl]methyl}phenyl)(1,3,4-thiadiazol-2-yl)]amine
3-{5-[(3-bromophenyl)amino]-1,3,4-thiadiazol- -yl}benzoic acid
(3-nitrophenyl)[5-(3-nitrophenyl)(1,3,4-thiadiazol- 2-yl)]amine
(2-chloro-5-nitrophenyl)[5-(3-ethoxyphenyl)(1,3,4- thiadiazol-2-yl)]amine
[5-(3-methoxyphenyl)(1,3,4-thiadiazol-2-yl)](3- nitrophenyl)amine
[5-(3-ethoxyphenyl)(1,3,4-thiadiazol-2-yl)](3- nitrophenyl)amine
[5-(3-methylphenyl)(1,3,4-thiadiazol-2-yl)](3- nitrophenyl)amine
Deleted Entry
[5-(3-nitrophenyl)(1,3,4-thiadiazol-2-yl)][3- (trifluoromethyl)phenyl]amine
(3-methoxyphenyl)[5-(3-nitrophenyl)(1,3,4-thia- diazol-2-yl)]amine
(4-nitrophenyl)[5-(3-nitrophenyl)(1,3,4-thia- diazol-2-yl)]amine
(4-ethylphenyl)[5-(3-nitrophenyl)(1,3,4-thia- diazol-2-yl)]amine
(3,4-dichlorophenyl){5-[3,5-bis(phenyl- methoxy)phenyl](1,3,4-thiadiazol-2-yl)}-amine
[3-(phenylmethoxy)phenyl](5-{3-[3-(tri- fluoromethyl)phenoxy]phenyl}(1,3,4-thidiazol-2-yl))amine
(5-benzo[c]1,2,5-oxadiazol-5-yl(1,3,4-thia- diazol-2-yl))(3,4-dichlorophenyl)amine
(5-benzo[3,4-c]1,2,5-oxadiazol-5-yl(1,3,4-thia- diazol-2-yl))(2,3-dichlorophenyl)amine
[5-({2-[(4,5-dichloroimidazolyl)methyl]phen- oxy}methyl)(1,3,4-thiadiazol-2-yl)](4-bromo-3-chlorophenyl)amine
Deleted Entry
(4-{[5-(3-ethoxyphenyl)(1,3,4-thiadiazol-2 -yl)]amino}phenyl)(phenylsulfonyl)amine
[(4-methylphenyl)sulfonyl](4-{[5-(3- nitrophenyl)(1,3,4-thiadiazol-2-yl)amino}phenyl)amine
(3,4-dibromophenyl)[5-(3,5-dimethoxyphenyl)- (1,3,4-thiadiazol-2-yl)]amine
(2,3-dichlorophenyl)[5-(3-nitrophenyl)(1,3,4- thiadiazol-2-yl)]amine
methyl 3-{[5-(3-nitrophenyl)-1,3,4-thia- diazol-2-yl]amino}benzoate
(3-bromophenyl)[5-(3-ethoxyphenyl)(1,3,4-thia- diazol-2-yl)]amine
(4-bromo-3-chlorophenyl)[5-(3-methoxyphenyl)- (1,3,4-thiadiazol-2-yl)]amine
(3-chloro-4-fluorophenyl)[5-(3-ethoxyphenyl)- (1,3,4-thiadiazol-2-yl)]amine
(4-bromo-3-methylphenyl)[5-(3-ethoxyphenyl)- (1,3,4-thiadiazol-2-yl)]amine
(4-bromo-3-methylphenyl)[5-(3-methoxyphenyl)- (1,3,4-thiadiazol-2-yl)]amine
(4-bromo-3-methylphenyl)[5-(3-nitrophenyl)- (1,3,4-thiadiazol-2-yl)]amine
(3-chloro-4-fluorophenyl)[5-(3-methoxyphenyl)- (1,3,4-thiadiazol-2-yl)]amine
(3-chloro-4-fluorophenyl)[5-(3-nitrophenyl)- (1,3,4-thiadiazol-2-yl)]amine
Deleted Entry
(4-bromo-3-chlorophenyl)[5-(3-ethoxyphenyl)- (1,3,4-thiadiazol-2-yl)]amine
(4-bromophenyl)[5-(3-nitrophenytl)(1,3,4-thia- diazol-2-yl)]amine
(2,5-dibromophenyl)[5-(3-nitrophenyl)(1,3,4-thia- diazol-2-yl)]amine
(3-bromophenyl)[5-(3-methoxyphenyl)(1,3,4-thia- diazol-2-yl)]amine
(3-bromophenyl)[5-(3-nitrophenyl)(1,3,4-thia- diazol-2-yl)]amine
ammonium 3-{4-[5-({3-[(2-phenylphenyl)- methylthio]phenyl}amino)(1,3,4-thiadiazol-2-yl)]phenyl}prop-2-enoate
ethyl 2-[(1Z)-1-aza-2-(3-{5-[(3,4-dichloro- phenyl)amino](1,3,4-thiadiazol-2-yl)}phenyl)-2-[3-(trifluoromethyl)phenyl]vinyloxy]acetate
3-({5-[3,5-bis(phenylmethoxy)phenyl]-1,3,4- thiadiazol-2-yl}amino)benzoic acid
(1-(2-[aza(3,4-dichlorophenyl)methylene]-3 -{[4-(tert-butyl)phenyl]methyl}(1,3,4-thiadiazolin-5-yl))-3-ethoxybenzene)
Structure
Name
Compound #
3-{3-[5-(3,4-Dichloro- phenylimino)-4-methyl-4,5- dihydro-[1,3,4]thiadiazol-2- yl]-phenoxy}-benzoic acid
164
4-{N′-[1-(3-{5-[3-(3- Trifluoromethyl-phenoxy)- phenyl]-[1,3,4]thiadiazol-2- ylamino}-phenyl)-ethylidene]- hydrazino}-benzoic acid
165
4-{[5-(3-Phenoxy-phenyl)- [1,3,4]thiadiazol-2-ylamino]- methyl}-benzoic acid
166
3,4[thiadiazol-2-yl]-amino}- methyl)-phenyl]-oxalamicacid
167
4-{[(4-Biphenyl-4-yl-thiazol- 2-yl)-(3,4-dichloro-phenyl)- amino]-methyl}-benzoic acid
168
N-{4-[((3,4-Dichloro-phenyl)- {5-[3-(3-trifluoromethyl- phenoxy)-phenyl]- [1,3,4]thiadiazol-2yl}-amino)- methyl]-phenyl}-oxalamic acid
169
(4-{2-(3,4-Dichloro- phenylimino)-5-[3-(3- trifluoromethyl-phenoxy)- phenyl]-[1,3,4]thiadiazol-3-yl- methyl}-phenyl)- acetic acid
170
4-[5-(3-{3-[5-(3,4-Dichloro- phenylamino)- [1,3,4]thiadiazol-2-yl]- phenoxy}-phenyl)-tetrazol-1- yl]-butyric acid
171
4-[N′-(3-{3-[5-(3,4-Dichloro- phenylamino)- [1,3,4]thiadiazol-2-yl]- phenoxy}-benzylidene)- hydrazino]-benzoic acid
172
7-(3-{3-[5-(3,4-Dichloro- phenylamino)- [1,3,4]thiadiazol- 2yl]-phenoxy}-phenyl)-hept- 6-enoic acid
173
4-[2-(3,4-Dichloro- phenylimino)-5-(4-phenoxy- phenyl)-[1,3,4]thiadiazol-3- ylmethyl]-benzoic acid.
174
[4-(Piperidine-1-sulfonyl)- phenyl]-[4-(4-pyrrolidin-1-yl- phenyl)-thiazol-2-yl]-amine
175
4-({(3,4-Dichloro-phenyl)- [4-(4-pyrrolidin-1-yl-phenyl)- thiazol-2-yl]-amino}-methyl)- benzoic acid
176
4-{3-[5-((3-(3- Hydroxycarbonylbenzyl)-5- Benzyloxy-phenyl)- [1,3,4]thiadiazol-2-ylamino]- phenylsulfanylmethyl}- benzoic acid
177
4-[4-(4-hydroxycarbonyl- benzyl)-5-(3,4-dichloro- phenylimino)-4,5-dihydro- [1,3,4]thiadiazol-2-yl]benzoic acid
178
4-({(4-Hydroxycarbonyl- benzyl-[5-(3-phenoxy- phenyl)-[1,3,4]thiadiazol- 2-yl]-amino}-methyl)- benzoic acid
179
4-[2-(3-Bromo-phenylimino)- 5-(3-nitro-phenyl)- [1,3,4]thiadiazol-3-ylmethyl]- benzoic acid
180
3-(3-{5-[(4-Hydroxycarbonyl- benzyl)-(3,4-dichloro-phenyl)- amino]-[1,3,4]thiadiazol-2- yl}-phenoxy)-benzoic acid
181
{2-(3,4-Dichloro- phenylimino)-5-[3-(3- trifluoromethyl-phenoxy)- phenyl]-[1,3,4]thiadiazol-3- yl}-acetic acid
182
((3,4-Dichloro-phenyl)-{5- [3-(3-tifluoromethyl- phenoxy)-phenyl]- [1,3,4]thiadiazol-2-yl}- amino)-acetic acid
183
4-[2-(3,4-Dichloro- phenylimino)-5-(3-phenoxy- phenyl)-[1,3,4]thiadiazol-3- ylmethyl]-benzoic acid
184
4-[2-Isopropylimino-5-(3- phenoxy-phenyl)- [1,3,4]thiadiazol-3-ylmethyl]- benzoic acid
185
4-{5-(3-Ethoxy-phenyl)-2-[4- (piperidine-1-sulfonyl)- phenylimino]- [1,3,4]thiadiazol-3-ylmethyl}- benzoic acid
186
4-{2-(3,4-Dichloro- phenylimino)-5-[3{3- trifluoromethyl-phenoxy)- phenyl]-[1,3,4]thiadiaziol-3- ylmethyl}-benzoic acid
187
3-[5-(3,5-Bis-benzyloxy- phenyl)-[1,3,4]thiadiazol-2- ylamino]-benzoic acid
188
3-[5-(3,5-Bis-benzyloxy- phenyl)-[1,3,4]thiadiazol-2- ylamino]-phenol
189
[1-(3-{5-[3-(3- Trifluoromethyl-phenoxy)- phenyl]-[1,3,4]thiadiazol-2- ylamino}-phenyl)- ethylideneaminooxy]acetic acid
190
4-[N′-(3-{3-[5-(3,4-Dichloro- phenylimino-4-methyl-4,5- dihydro-[1,3,4]thiadiazol-2- yl]-phenoxy}-benzylidene)- hydrazino]-benzoic acid
191
4-{N′[3-{5-[(3,4-Dichloro- phenyl)-methyl-amino)- [1,3,4]thiadiazol-2-yl}- phenoxy)-benzylidene[- hydrazino}-benzoic acid
192
5-[5-(3-{3-[5-(3,4-Dichoro- phenylamino)- [1,3,4]thiadiazol-2-yl]- phenoxy}-phenyl)-tetrazol-1- yl]-pentanoic acid
193
4-{N′-[{3-[5-(3,4-Dichloro- phenylamino)- [1,3,4]thiadiazol2-yl]- phenyl}-(3-trifluoromethyl- phenyl)-methylene]- hydrazino}-benzoic acid
194
3-(3-Benzyloxy-5-{5-[3-(5- carboxy-pentylsulfanyl)- phenylamino]- [1,3,4]thiadiazol-2-yl}- phenoxymethyl)-benzoic acid
195
{3-[5-(3,4-Dichloro- phenylamino)- [1,3,4]thiadiazol-2-yl]- phenyl}-(3-trifluoromethyl- phenyl)-methylsulfanyl]- acetic acid
196
3-{5-[3,5-Bis-(3-methoxy- phenoxy)-phenyl]- [1,3,4]thiadiazol-2- ylamino}-benzoic acid
197
3-{5-[3,5-Bis-(3- trifluoromethyl-phenoxy)- phenyl]-[1,3,4]thiadiazol-2- ylamino}-benzoic acid
198
[2-(3-{3-[5-(3,4-Dichloro- phenylamino)- [1,3,4]thiadiazol-2-yl]- phenoxy}-phenyl)-1,1- difluoro-2-hydroxy-ethyl]- phosphonic acid
199
{5-[2-(4-Bromo-3-chloro- phenylimino)-5-(3-ethoxy- phenyl)-[1,3,4]thiadiazol-3- yl]-1,1-difluoro-pentyl}- phosphonic acid
200
[(4-{3-[5-(3,4-Dichloro- phenylimino)-4-methyl-4,5- dihydro-[1,3,4]thiadiazol-2- yl]-phenoxy}-phenyl)- difluoro-methyl]- phosphonic acid
201
{[4-({(3,4-Dichloro- phenyl)-[5-(3-phenoxy- phenyl)-[1,3,4]thiadiazol-2- yl]-amino}-methyl)-phenyl]- difluoro-methyl}- phosphonic acid
202
({4-[2-(3,4-Dichloro- phenylimino)-5-(3-phenoxy- phenyl)-[1,3,4]thiadiazol-3- ylmethyl]-phenyl}-difluoro- methyl)-phosphonic acid
203
4-({[4-(Difluoro-phosphono- methyl)-benzyl]-[5-(3- phenoxy-phenyl)- [1,3,4]thiadiazol-2-yl]- amino}-methyl)-benzoic acid
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